Articles tagged as "Epidemiology"

How many people have really died of HIV/AIDS in South Africa?

HIV/AIDS in South Africa: how many people died from the disease between 1997 and 2010?

Bradshaw D, Msemburi W, Dorrington R, Pillay-van Wyk V, Laubscher R, Groenewald P, team SN. AIDS. 2015 Oct 27. [Epub ahead of print]

Objectives: Empirical estimates of the number of HIV/AIDS deaths are important for planning, budgeting, and calibrating models. However, there is an extensive misattribution of HIV/AIDS as an underlying cause-of-death. This study estimates the true numbers of AIDS deaths from South African vital statistics between 1997 and 2010.

Methods: Individual-level cause-of-death data were grouped according to a local burden of disease list and source causes (i.e. causes under which AIDS deaths are misclassified) that recorded a rapid increase. After adjusting for completeness of registration, mortality rate of the source causes, by age and sex, was regressed on lagged HIV prevalence to estimate the rate of increase correlated with HIV. Background trends in the source-cause mortality rates were estimated from the trend experienced among 75-84 year olds.

Results: Of 214 causes considered, 19 were identified as potential sources for cause misattribution. High proportions of deaths from tuberculosis, lower respiratory infections (mostly pneumonia), diarrhoeal diseases, and ill-defined natural causes were estimated to be HIV-related, with only 7% of the estimated AIDS deaths being recorded as HIV. Estimated HIV/AIDS deaths increased rapidly, then reversed after 2006, totalling 2.8 million deaths over the whole period. The number was lower than model estimates from UNAIDS and the Global Burden of Disease Study.

Conclusion: Empirically based estimates confirm the considerable loss of life from HIV/AIDS and should be used for calibrating models of the AIDS epidemic which generally appear too low for infants but too high for other ages. Doctors are urged to specify HIV on death notifications to provide reliable cause-of-death statistics.

Abstract access 

Editor’s notesIn many countries, the true number of HIV-associated deaths is significantly under-reported in national vital registration data making it difficult to monitor the epidemic trends from this source. This study describes new estimates of HIV-associated mortality based on empirical vital registration data which aimed to provide accurate estimates of the numbers of HIV-associated deaths in South Africa. The study estimates that, from 1997-2010, 2.86 million deaths in South Africa were due to HIV – over one-third of all deaths. However, relatively few deaths, 7%, were registered as HIV-associated. At the peak of the epidemic in 2006 the vital registration derived estimates show lower trends than other models. All models estimated a decline in the number of HIV-associated deaths post-2008, a finding which is consistent with the extensive roll-out of antiretroviral therapy in South Africa, and with trends reported from verbal autopsy data for all deaths in rural South African demographic surveillance sites. This paper highlights the importance of reporting accurate causes for HIV-associated deaths in the death registration process - however, without de-stigmatisation of HIV, this is going to be difficult to achieve.

Africa
South Africa
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Intimate partner violence and uptake and adherence of HIV treatment

Intimate partner violence and engagement in HIV care and treatment among women: a systematic review and meta-analysis.

Hatcher AM, Smout EM, Turan JM, Christofides N, Stockl H. AIDS. 2015 Sep 5. [Epub ahead of print]

Objective: We aimed to estimate the odds of engagement in HIV care and treatment among HIV-positive women reporting intimate partner violence (IPV).

Design: We systematically reviewed the literature on the association between IPV and engagement in care. Data sources included searches of electronic databases (PubMed, Web of Science, CINAHL and PsychoInfo), hand searches and citation tracking.

Methods: Two reviewers screened 757 full-text articles, extracted data and independently appraised study quality. Included studies were peer-reviewed and assessed IPV alongside engagement in care outcomes: antiretroviral treatment (ART) use; self-reported ART adherence; viral suppression; retention in HIV care. Odds ratios (ORs) were pooled using random effects meta-analysis.

Results: Thirteen cross-sectional studies among HIV-positive women were included. Measurement of IPV varied, with most studies defining a 'case' as any history of physical and/or sexual IPV. Meta-analysis of five studies showed IPV to be significantly associated with lower ART use [OR 0.79, 95% confidence interval (95% CI) 0.64-0.97]. IPV was associated with poorer self-reported ART adherence in seven studies (OR 0.48, 95% CI 0.30-0.75) and lower odds of viral load suppression in seven studies (OR 0.64, 95% CI 0.46-0.90). Lack of longitudinal data and measurement considerations should temper interpretation of these results.

Conclusion: IPV is associated with lower ART use, half the odds of self-reported ART adherence and significantly worsened viral suppression among women. To ensure the health of HIV-positive women, it is essential for clinical programmes to address conditions that impact engagement in care and treatment. IPV is one such condition, and its association with declines in ART use and adherence requires urgent attention.

Abstract access 

Editor’s notes: Intimate partner violence (IPV) is prevalent globally (30%). It has been associated with HIV infection and also with progression to AIDS among women living with HIV. However it is unclear how intimate partner violence may impact on HIV-associated health. This study examined associations between violence exposure and uptake of HIV treatment and care services. The authors conducted a systematic review and meta-analyses. From an initial search of 621 studies, 13 were included in these analyses: 12 were conducted in the United States of America and one in Haiti. All were cross-sectional. Measurement of intimate partner violence varied from a single question to validated scales. Some 11 measured lifetime IPV and two measured recent intimate partner violence, in the past 12 months.

Meta-analysis suggests intimate partner violence is associated with significantly lower odds of (i) current ART use (ii) self-reported adherence and (iii) worsened viral load suppression. There was insufficient data to measure retention in HIV care. These analyses suggest that uptake and adherence to ART is a key pathway through which intimate partner violence may negatively influence HIV-associated health of women. Further research is necessary, in low and middle income settings, and among key populations. Future studies should develop and test programmes to address intimate partner violence within HIV clinical care. 

Latin America, Northern America
Haiti, United States of America
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Tenofovir vaginal gel offers significant protection against HSV-2 infection

Tenofovir gel for the prevention of herpes simplex virus type 2 infection.

Abdool Karim SS, Abdool Karim Q, Kharsany AB, Baxter C, Grobler AC, Werner L, Kashuba A, Mansoor LE, Samsunder N, Mindel A, Gengiah TN, Group CT. N Engl J Med. 2015 Aug 6;373(6):530-9. doi: 10.1056/NEJMoa1410649.

Background: Globally, herpes simplex virus type 2 (HSV-2) infection is the most common cause of genital ulcer disease. Effective prevention strategies for HSV-2 infection are needed to achieve the goals of the World Health Organization global strategy for the prevention and control of sexually transmitted infections.

Methods: We assessed the effectiveness of pericoital tenofovir gel, an antiviral microbicide, in preventing HSV-2 acquisition in a subgroup of 422 HSV-2-negative women enrolled in the Centre for the AIDS Programme of Research in South Africa (CAPRISA) 004 study, a double-blind, randomized, placebo-controlled trial. Incident HSV-2 cases were identified by evidence of seroconversion on an HSV-2 IgG enzyme-linked immunosorbent assay between study enrollment and exit. A confirmatory analysis was performed by Western blot testing.

Results: The HSV-2 incidence rate was 10.2 cases per 100 person-years (95% confidence interval [CI], 6.8 to 14.7) among 202 women assigned to tenofovir gel, as compared with 21.0 cases per 100 person-years (95% CI, 16.0 to 27.2) among 222 women assigned to placebo gel (incidence rate ratio, 0.49; 95% CI, 0.30 to 0.77; P=0.003). The HSV-2 incidence rate among the 25 women with vaginal tenofovir concentrations of 10 000 ng per milliliter or more was 5.7 cases per 100 person-years, as compared with 15.5 cases per 100 person-years among the 103 women with no detectable vaginal tenofovir (incidence rate ratio, 0.37; 95% CI, 0.04 to 1.51; P=0.14). As confirmed by Western blot testing, there were 16 HSV-2 seroconversions among women assigned to tenofovir gel as compared with 36 among those assigned to the placebo gel (incidence rate ratio, 0.45; 95% CI, 0.23 to 0.82; P=0.005).

Conclusions: In this study in South Africa, pericoital application of tenofovir gel reduced HSV-2 acquisition in women.

Abstract access 

Editor’s notes: Oral tenofovir is widely used to prevent and treat HIV infection, but application of a topical tenofovir vaginal-gel formulation has not been found to be protective against HIV, likely because of low rates of adherence. In contrast, analyses of tenofovir gel protection against HSV-2, herpes simplex virus, has showed some promise. This paper presents additional data and analyses from the CAPRISA004 study which found the modest effect of protection against HIV, but significant protection against HSV-2 (51% effectiveness). A sub-analysis confirmed that those people with higher vaginal tenofovir concentrations were almost three times less likely to acquire the herpes virus than those people with no detectable drug concentration. In the absence of an effective vaccine or cure for HSV-2 infection, pericoital tenofovir gel has the potential to increase the options for HSV-2 prevention, and have an indirect effect on HIV infection. 

Africa
South Africa
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Antiretroviral therapy coverage associated with reduced HIV incidence in Kenya

Impact of community antiretroviral therapy coverage on HIV incidence in Kenyan female sex workers: a 15-year prospective cohort study.

McClelland RS, Richardson BA, Cherutich P, Mandaliya K, John-Stewart G, Miregwa B, Odem-Davis K, Jaoko W, Kimanga D, Overbaugh J. AIDS. 2015 Jul 31. [Epub ahead of print]

Objective: To test the hypothesis that increasing community antiretroviral therapy (ART) coverage would be associated with lower HIV incidence in female sex workers (FSWs) in Mombasa District, Kenya.

Design: Prospective cohort study.

Methods: From 1998 to 2012, HIV-negative FSWs were asked to return monthly for an interview regarding risk behavior and testing for sexually transmitted infections including HIV. We evaluated the association between community ART coverage and FSW's risk of becoming HIV infected using Cox proportional hazards models adjusted for potential confounding factors.

Results: One thousand four hundred four FSWs contributed 4335 woman-years of follow-up, with 145 acquiring HIV infection (incidence 3.35/100 woman-years). The ART rollout began in 2003. By 2012, an estimated 52% of HIV-positive individuals were receiving treatment. Community ART coverage was inversely associated with HIV incidence (adjusted hazard ratio 0.77; 95% confidence interval 0.61-0.98; P = 0.03), suggesting that each 10% increase in coverage was associated with a 23% reduction in FSWs' risk of HIV acquisition. Community ART coverage had no impact on herpes simplex virus type-2 incidence (adjusted hazard ratio 0.97; 95% confidence interval 0.79-1.20; P = 0.8).

Conclusion: Increasing general population ART coverage was associated with lower HIV incidence in FSWs. The association with HIV incidence, but not herpes simplex virus type-2 incidence, suggests that the effect of community ART coverage may be specific to HIV. Interventions such as preexposure prophylaxis and antiretroviral-containing microbicides have produced disappointing results in HIV prevention trials with FSWs. These results suggest that FSWs' risk of acquiring HIV infection might be reduced through the indirect approach of increasing ART coverage in the community.

Abstract access

Editor’s notes: The individual-level benefit of antiretroviral therapy (ART) on reducing HIV transmission between serodiscordant partners is established, but less is known about a possible population-level effect of ART on key populations such as female sex workers. In this study of 1404 initially HIV-negative female sex workers in Mombasa, Kenya, increased community ART coverage was strongly associated with reduced HIV incidence. HIV incidence was 23% lower for every 10% increase in ART coverage, after adjusting for HIV prevalence and participants’ behavioural characteristics. However, the authors note that HIV incidence was already declining prior to the introduction of ART (from 11.4 cases/100 woman-years in 1998 to 7.6/100 woman-years in 2002), due to other factors including changes in risk behaviour and HIV-prevention efforts in the community. Despite this, the present study suggests that in the setting of ongoing high-quality HIV prevention services, the risk of HIV acquisition among female sex workers is likely to be reduced by increasing ART coverage in the community. Moves to increase coverage of ART in the community will potentially have a substantial HIV prevention benefit on this key population.

Africa
Kenya
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Understanding delays in TB diagnosis: where do people go before accessing TB services?

Four degrees of separation: social contacts and health providers influence the steps to final diagnosis of active tuberculosis patients in urban Uganda.

Sekandi JN, Zalwango S, Martinez L, Handel A, Kakaire R, Nkwata AK, Ezeamama AE, Kiwanuka N, Whalen CC. BMC Infect Dis. 2015 Aug 21;15:361. doi: 10.1186/s12879-015-1084-8.

Background: Delay in tuberculosis (TB) diagnosis adversely affects patients' outcomes and prolongs transmission in the community. The influence of social contacts on steps taken by active pulmonary TB patients to seek a diagnosis has not been well examined.

Methods: A retrospective study design was use to enroll TB patients on treatment for 3 months or less and aged ≥18 years from 3 public clinics in Kampala, Uganda, from March to July 2014. Social network analysis was used to collect information about social contacts and health providers visited by patients to measure the number of steps and time between onset of symptoms and final diagnosis of TB.

Results: Of 294 TB patients, 58% were male and median age was 30 (IQR: 24-38) years. The median number of steps was 4 (IQR: 3, 7) corresponding to 70 (IQR: 28,140) days to diagnosis. New patients had more steps and time to diagnosis compared retreatment patients (5 vs. 3, P < 0.0001; 84 vs. 46 days P < 0.0001). Fifty-eight percent of patients first contacted persons in their social network. The first step to initiate seeking care accounted for 41 % of the patients' time to diagnosis while visits to non-TB providers and TB providers (without a TB diagnosis) accounted for 34 % and 11 % respectively. New TB patients vs. retreatment (HR: 0.66, 95 % CI; 1.11, 1.99), those who first contacted a non-TB health provider vs. contacting social network (HR: 0.72 95 % CI; 0.55, 0.95) and HIV seronegative vs. seropositive patients (HR: 0.70, 95 % CI; 0.53, 0.92) had a significantly lower likelihood of a timely final diagnosis.

Conclusions: There were four degrees of separation between the onset of symptoms in a TB patient and a final diagnosis. Both social and provider networks of patients influenced the diagnostic pathways. Most delays occurred in the first step which represents decisions to seek help, and through interactions with non-TB health providers. TB control programs should strengthen education and active screening in the community and in health care settings to ensure timely diagnosis of TB.

Abstract  Full-text [free] access

Editor’s notes: Delays in tuberculosis diagnosis are well documented in the literature and barriers to diagnosis exist in the community and the health system. This study, in an urban setting in Uganda, included a more in-depth exploration of the steps people take when symptomatic before receiving a TB diagnosis. The median time from onset of symptoms to diagnosis was over two months and the majority of people sought help from relatives and friends and non-TB providers (e.g. private clinics or pharmacies) before accessing public health facilities. There was evidence that having been treated for TB previously reduced the delay, suggesting that existing knowledge of TB in these cases may have influenced their health-seeking behaviour. It was also of interest that delays to diagnosis were greater in HIV-negative people, although it was not possible to establish whether that related to different access to care or to different patterns or severity of symptoms. This is of particular interest because it is thought that in communities with high HIV prevalence, most TB transmission may be attributable to HIV-negative people with active TB.

This study highlights the potential risk of TB transmission in the community during the pre-diagnostic phase. It seems clear that to interrupt TB transmission we need to develop programmes that go beyond public health facilities and this underlines the need for broad community engagement and education as well as more focused programmes to facilitate links between other health care providers and TB services. It is also important to remember that to interrupt transmission we must ensure that TB services and programmes are accessible to HIV-negative people as well as people living with HIV. 

Avoid TB deaths
Africa
Uganda
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DMPA contraception users more likely than NET-EN users to acquire HIV in South Africa

Risk of HIV-1 acquisition among women who use different types of injectable progestin contraception in South Africa: a prospective cohort study.

Noguchi LM, Richardson BA, Baeten JM, Hillier SL, Balkus JE, Chirenje ZM, Bunge K, Ramjee G, Nair G, Palanee-Phillips T, Selepe P, van der Straten A, Parikh UM, Gomez K, Piper JM, Watts DH, Marrazzo JM. Lancet HIV. 2015 Jul 1;2(7):e279-e287.

Background: Several observational studies have reported that HIV-1 acquisition seems to be higher in women who use depot medroxyprogesterone acetate (DMPA) than in those who do not use hormonal contraception. We aimed to assess whether two injectable progestin-only contraceptives, DMPA and norethisterone enanthate (NET-EN), confer different risks of HIV-1 acquisition.

Methods: We included data from South African women who used injectable contraception while participating in the VOICE study, a multisite, randomised, placebo-controlled trial that investigated the safety and efficacy of three formulations of tenofovir for prevention of HIV-1 infection in women between Sept 9, 2009, and Aug 13, 2012. Women were assessed monthly for contraceptive use and incident infection. We estimated the difference in incident HIV-1 infection between DMPA and NET-EN users by Cox proportional hazards regression analyses in this prospective cohort. The VOICE trial is registered with ClinicalTrials.gov, NCT00705679.

Findings: 3141 South African women using injectable contraception were included in the present analysis: 1788 (56.9%) solely used DMPA, 1097 (34.9%) solely used NET-EN, and 256 (8.2%) used both injectable types at different times during follow-up. During 2733.7 person-years of follow-up, 207 incident HIV-1 infections occurred (incidence 7.57 per 100 person-years, 95% CI 6.61-8.68). Risk of HIV-1 acquisition was higher among DMPA users (incidence 8.62 per 100 person-years, 95% CI 7.35-10.11) than among NET-EN users (5.67 per 100 person-years, 4.35-7.38; hazard ratio 1.53, 95% CI 1.12-2.08; p=0.007). This association persisted when adjusted for potential confounding variables (adjusted hazard ratio [aHR] 1.41, 95% CI 1.06-1.89; p=0.02). Among women seropositive for herpes simplex virus type 2 (HSV-2) at enrolment, the aHR was 2.02 (95% CI 1.26-3.24) compared with 1.09 (0.78-1.52) for HSV-2-seronegative women (pinteraction=0.07).

Interpretation: Although moderate associations in observational analyses should be interpreted with caution, these findings suggest that NET-EN might be an alternative injectable drug with a lower HIV risk than DMPA in high HIV-1 incidence settings where NET-EN is available.

Abstract access

Editor’s notes: In eastern and southern Africa, injectable methods are the most popular contraceptives. But evidence that the injectable progestin depot medroxyprogesterone acetate (DMPA) is associated with an increased risk of HIV-1 acquisition means that alternative injectable contraceptive methods are necessary. This large prospective study used data from the VOICE HIV prevention trial, analysing data from South Africa on 3141 women who had used one of two progestin methods for contraception. HIV incidence was high in the population (7.57/100 person-years overall), and participants who used DMPA were 40% more likely to become HIV positive than women who used norethisterone enanthate (NET-EN) after adjustment for demographic and behavioural confounding variables. Strengths of this study include the comparability across women using progestin methods, and its frequent follow up visits to assess HIV status, contraception use, sexual behaviour and the presence of reproductive tract infections. The results suggest NET-EN might be an alternative injectable contraceptive with a lower risk for HIV-1 acquisition than DMPA.

Africa
South Africa
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Switching to second-line ART – we need to do better

Monitoring and switching of first-line antiretroviral therapy in sub-Saharan Africa: collaborative analysis of adult treatment cohorts.

Haas AD, Keiser O, Balestre E, Brown S, Bissagnene E, Chimbetete C, Dabis F, Davies MA, Hoffmann CJ, Oyaro P, Parkes-Ratanshi R, Reynolds SJ, Sikazwe I, Wools-Kaloustian K, Zannou DM, Wandeler G, Egger M, for IeDea Southern Africa EA, West A. Lancet HIV. 2015 Jul 1;2(7):e271-e278.

Background: HIV-1 viral load testing is recommended to monitor antiretroviral therapy (ART) but is not universally available. The aim of our study was to assess monitoring of first-line ART and switching to second-line ART in sub-Saharan Africa.

Methods: We did a collaborative analysis of cohort studies from 16 countries in east Africa, southern Africa, and west Africa that participate in the international epidemiological database to evaluate AIDS (IeDEA). We included adults infected with HIV-1 who started combination ART between January, 2004, and January, 2013. We defined switching of ART as a change from a non-nucleoside reverse-transcriptase inhibitor (NNRTI)-based regimen to one including a protease inhibitor, with adjustment of one or more nucleoside reverse-transcriptase inhibitors (NRTIs). Virological and immunological failures were defined according to WHO criteria. We calculated cumulative probabilities of switching and hazard ratios with 95% CIs comparing routine viral load monitoring, targeted viral load monitoring, CD4 monitoring, and clinical monitoring, adjusting for programme and individual characteristics.

Findings: Of 297 825 eligible patients, 10 352 (3%) switched to second-line ART during 782 412 person-years of follow-up. Compared with CD4 monitoring, hazard ratios for switching were 3·15 (95% CI 2·92–3·40) for routine viral load monitoring, 1·21 (1·13–1·30) for targeted viral load monitoring, and 0·49 (0·43–0·56) for clinical monitoring. Of 6450 patients with confirmed virological failure, 58·0% (95% CI 56·5–59·6) switched by 2 years, and of 15 892 patients with confirmed immunological failure, 19·3% (18·5–20·0) switched by 2 years. Of 10 352 patients who switched, evidence of treatment failure based on one CD4 count or viral load measurement ranged from 86 (32%) of 268 patients with clinical monitoring to 3754 (84%) of 4452 with targeted viral load monitoring. Median CD4 counts at switching were 215 cells per μL (IQR 117–335) with routine viral load monitoring, but were lower with other types of monitoring (range 114–133 cells per μL).

Interpretation: Overall, few patients switched to second-line ART and switching happened late in the absence of routine viral load monitoring. Switching was more common and happened earlier after initiation of ART with targeted or routine viral load testing.

Abstract access 

Editor’s notes: Routine viral load monitoring should allow the early identification of first-line antiretroviral therapy (ART) failure, allowing prompt switch to second-line ART. Prolongation of treatment with a failing regimen compromises future therapeutic options (through the accumulation of drug resistance mutations) and potentially leads to increased morbidity and mortality. Previous reports from Africa have suggested that surprisingly few people switch to second-line therapy, even in programmes with routine viral load monitoring. This raises concerns that there are challenges on the ground with identification and management of ART failure.

This is a comprehensive analysis bringing together data from a number of well-characterised cohorts in Africa. In this analysis, switching to second-line ART was rare (3% over an average of almost three years follow-up). In programmes with routine viral load monitoring, only half of the people with confirmed virologic failure on first-line ART (two viral loads >1000 copies/ml) were recorded as having been switched to second-line ART. Furthermore, half of the people that were switched to a second-line regimen did not have evidence of confirmed virologic failure, suggesting that some may have been switched too early without first attempting adherence programmes which may achieve re-suppression on first-line ART. Unsurprisingly, rates of switching were lower in programmes with CD4+ monitoring (with or without targeted viral load testing) or clinical monitoring alone. 

While guidelines and algorithms around identification and management of first-line ART failure are relatively clear and straightforward, translating this into action on the ground seems to be difficult. At least part of this is likely to be due to the lack of tools to reliably measure adherence and the consequent difficulty that frontline health care workers have in identifying people that truly require a switch to second-line ART. Moreover, most programmes still do not routinely monitor indicators relating to virologic suppression or treatment failure and so this might not be seen as a priority by health care workers and programme managers. There is a need for research to explore how best to maximise virologic suppression in resource-constrained settings, as well as studies to evaluate the impact of programmes such as point-of-care viral load testing.

Africa
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Where are the weak links in prevention of mother-to-child HIV transmission programmes?

Reconstructing the PMTCT cascade using cross-sectional household survey data: The PEARL Study.

Chi BH, Tih PM, Zanolini A, Stinson K, Ekouevi DK, Coetzee D, Welty TK, Bweupe M, Shaffer N, Dabis F, Stringer EM, Stringer JS. J Acquir Immune Defic Syndr. 2015 Jun 11. [Epub ahead of print]

Background: Given the ambitious targets to reduce pediatric AIDS worldwide, ongoing assessment of programs to prevent mother-to-child HIV transmission (PMTCT) is critical. The concept of a "PMTCT cascade" has been used widely to identify bottlenecks in program implementation; however, most efforts to reconstruct the cascade have relied on facility-based approaches that may limit external validity.

Methods: We analyzed data from the PEARL household survey, which measured PMTCT effectiveness in 26 communities across Zambia, South Africa, Cote d'Ivoire, and Cameroon. We recruited women who reported a delivery in the past two years. Among mothers confirmed to be HIV-infected at the time of survey, we reconstructed the PMTCT cascade with self-reported participant information. We also analyzed data about the child's vital status; for those still alive, HIV testing was performed via DNA PCR.

Results: Of the 976 eligible women, only 355 (36%) completed every step of the PMTCT cascade. Among the 621 mother-child pairs who did not, 22 (4%) reported never seeking antenatal care, 103 (17%) were not tested for HIV during pregnancy, 395 (64%) reported testing but never received their HIV-positive result, 48 (8%) did not receive maternal antiretroviral prophylaxis, and 53 (9%) did not receive infant antiretroviral prophylaxis. The lowest prevalence of infant HIV infection or death was observed in those completing the cascade (10%, 95%CI: 7%-12%).

Conclusions: Future efforts to measure population PMTCT impact should incorporate dimensions explored in the PEARL Study - including HIV testing of HIV-exposed children in household surveys - to better understand program effectiveness.

Abstract access 

Editor’s notes: Programmes to prevent the transmission of HIV from mother-to-child can virtually eliminate transmission when conducted with adequate coverage and quality. This population-based study recruited women living with HIV who had given birth in the past 24 months from four sub-Saharan African countries including Cameroon, Côte d’Ivoire, South Africa and Zambia. The 976 mothers allowed their children to be tested for HIV, and reported on the level of maternal health services they received for that child, the “prevention of mother-to-child HIV transmission cascade”. While 98% of mothers had at least one contact with antenatal care services, only 36% eventually received services considered to be adequate for preventing transmission of HIV to their children. This study is notable for highlighting exactly where coverage gaps exist along the treatment pathway. In particular, 53% of mothers did not receive the result of an HIV test, and so would not have received follow-up services to prevent transmission. As a population-based study, these data provide a fuller picture of service coverage which cannot be captured by traditional monitoring and evaluations systems. These results can inform where systems strengthening must occur along the “prevention of mother-to-child HIV transmission cascade”, so that transmission risk is minimized for all children born to women living with HIV.

Africa
Cameroon, Côte d'Ivoire, South Africa, Zambia
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Xpert testing - rationalise with chest X-ray or HIV pre-screening?

Implementation research to inform the use of Xpert MTB/RIF in primary health care facilities in high TB and HIV settings in resource constrained settings.

Muyoyeta M, Moyo M, Kasese N, Ndhlovu M, Milimo D, Mwanza W, Kapata N, Schaap A, Godfrey Faussett P, Ayles H. PLoS One. 2015 Jun 1;10(6):e0126376. doi: 10.1371/journal.pone.0126376. eCollection 2015.

Background: The current cost of Xpert MTB RIF (Xpert) consumables is such that algorithms are needed to select which patients to prioritise for testing with Xpert.

Objective: To evaluate two algorithms for prioritisation of Xpert in primary health care settings in a high TB and HIV burden setting.

Method: Consecutive, presumptive TB patients with a cough of any duration were offered either Xpert or Fluorescence microscopy (FM) test depending on their CXR score or HIV status. In one facility, sputa from patients with an abnormal CXR were tested with Xpert and those with a normal CXR were tested with FM ("CXR algorithm"). CXR was scored automatically using a Computer Aided Diagnosis (CAD) program. In the other facility, patients who were HIV positive were tested using Xpert and those who were HIV negative were tested with FM ("HIV algorithm").

Results: Of 9482 individuals pre-screened with CXR, Xpert detected TB in 2090/6568 (31.8%) with an abnormal CXR, and FM was AFB positive in 8/2455 (0.3%) with a normal CXR. Of 4444 pre-screened with HIV, Xpert detected TB in 508/2265 (22.4%) HIV positive and FM was AFB positive in 212/1920 (11.0%) in HIV negative individuals. The notification rate of new bacteriologically confirmed TB increased; from 366 to 620/100 000/yr and from 145 to 261/100 000/yr at the CXR and HIV algorithm sites respectively. The median time to starting TB treatment at the CXR site compared to the HIV algorithm site was: 1(IQR 1-3 days) and 3 (2-5 days) (p<0.0001) respectively.

Conclusion: Use of Xpert in a resource-limited setting at primary care level in conjunction with pre-screening tests reduced the number of Xpert tests performed. The routine use of Xpert resulted in additional cases of confirmed TB patients starting treatment. However, there was no increase in absolute numbers of patients starting TB treatment. Same day diagnosis and treatment commencement was achieved for both bacteriologically confirmed and empirically diagnosed patients where Xpert was used in conjunction with CXR.

Abstract  Full-text [free] access

Editor’s notes: Although many countries have begun to deploy molecular TB diagnostics, the cost of these technologies remains prohibitive for widespread use in low- and middle-income countries. This study in Zambian primary health care clinics aimed to explore whether the use of Xpert® MTB/RIF could be rationalised by pre-screening individuals with cough, either by chest X-ray (CXR) or by HIV testing. CXR screening only marginally reduced the use of Xpert® (as three-quarters of people screened had an abnormal CXR, using digital X-ray and computerised interpretation). Restricting use of Xpert® to those known to be HIV-positive reduced the number of Xpert® tests by around half. Under both algorithms, the proportion testing Xpert® positive was very high (22-32%), suggesting that too few people were being identified as needing TB investigation. Similar to other studies of Xpert® implementation, the overall number of people starting TB treatment did not increase with the introduction of Xpert®. However, the proportion of people starting TB treatment who had microbiological confirmation did increase substantially under both algorithms. Empirical TB treatment (meaning initiation of treatment without microbiological confirmation) remained common, in the X-ray algorithm particularly where a third of people with an abnormal CXR but a negative Xpert® were started on TB treatment. This study was not designed to determine how many people who genuinely had TB were missed by each algorithm. Also this paper did not include cost-effectiveness analyses. Based on this evidence, neither of these algorithms can be clearly recommended. Further evaluation of different screening and testing strategies will be important to inform the scale-up of molecular diagnostics.   

Avoid TB deaths
Africa
Zambia
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Community-based rapid testing boosts case finding among MSM in China

Case finding advantage of HIV rapid tests in community settings: men who have sex with men in 12 programme areas in China, 2011.

Zhang D, Qi J, Fu X, Meng S, Li C, Sun J. Int J STD AIDS. 2015 May;26(6):402-13. doi: 10.1177/0956462414542986. Epub 2014 Jul 15.

We sought to describe the advantage of rapid tests over ELISA tests in community-based screening for HIV among men who have sex with men (MSM) in urban areas of China. Data of 31 406 screening tests conducted over six months in 2011 among MSM across 12 areas were analyzed to compare the differences between those receiving rapid testing and ELISA. Rapid tests accounted for 45.8% of these screening tests. The rate of being screened positive was 7.2% among rapid tests and 5.3% for ELISA tests (X(2)= 49.161, p < 0.001). This advantage of rapid test in HIV case finding persisted even when socio-demographic, behavioural, screening recruitment channel and city were controlled for in logistic regression (exp[beta] = 1.42, p < 0.001, 95% CI = 1.27,1.59). MSM who received rapid tests, compared with those tested by ELISA, were less likely to use condoms during last anal sex (50.8% vs. 72.3%, X(2)= 1706.146, p < 0.001), more likely to have multiple sex partners (55.7% vs. 49.5%, X(2)= 238.188, p < 0.001) and less likely to have previously undergone HIV testing (38.8% vs. 54.7%, X(2)= 798.476, p < 0.001). These results demonstrate the robustness of the advantage of rapid tests over traditional ELISA tests in screening for MSM with HIV infection in cooperation with community-based organizations in urban settings in China.

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Editor’s notes: The prevalence of HIV among gay men and other men who have sex with men in China has increased from 1% to 5% between 2006 and 2011. The increase in prevalence has motivated the development of a new HIV testing strategy to reach this key population. The China-Gates HIV Programme facilitated partnerships between local government health departments with community-based organizations (CBO) to reach and offer rapid HIV screening tests to gay men and other men who have sex with men in 14 cities and one province. Between July and December 2011, 17 015 men were tested through established HIV testing sites (run solely by the health departments, which used enzyme-linked immunosorbent assay [ELISA] testing) and another 14 391 men were tested at sites which were established, promoted, and run by the government-CBO partnerships. These sites used rapid HIV tests, and referred to the health department for confirmatory testing. After controlling for sociodemographic characteristics, transmission risk factors and geographic location, the odds of testing positive for HIV was 42% higher for men who were screened at partnership sites. This partnership demonstrates an innovative, culturally appropriate and scale-able model. For key populations, partnerships of this nature can lead to earlier treatment initiation and a reduction in secondary transmission.

Asia
China
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