Enhanced peer-group strategies to support the prevention of mother-to-child HIV transmission leads to increased retention in care in Uganda: A randomized controlled trial.

INTRODUCTION: Despite the scale-up of Option B+, long-term retention of women in HIV care during pregnancy and the postpartum period remains an important challenge. We compared adherence to clinic appointments and antiretroviral therapy (ART) at 6 weeks, 6, and and 24 months postpartum among pregnant women living with HIV and initiating Option B+. Women were randomized to a peer group support, community-based drug distribution and income-generating intervention called "Friends for Life Circles" (FLCs) versus the standard of care (SOC). Our secondary outcome was infant HIV status and HIV-free survival at 6 weeks and 18 months postpartum. METHODS: Between 16 May 2016 and 12 September 2017, 540 ART-naïve pregnant women living with HIV at urban and rural health facilities in Uganda were enrolled in the study at any gestational age. Participants were randomized 1:1 to the unblinded FLC intervention or SOC at enrolment and assessed for adherence to the prevention of mother-to-child HIV transmission (PMTCT) clinic appointments at 6 weeks, 12, and 24 months postpartum, self-reported adherence to ART at 6 weeks, 6 and 24 months postpartum and supported by plasma HIV-1 RNA viral load (VL) measured at the same time points, retention in care through the end of study, and HIV status and HIV-free survival of infants at 18 months postpartum. The FLC groups were formed during pregnancy within 4 months of enrollment and held monthly meetings in their communites, and were followed up until the last group participant reached 24 months post delivery. We used Log-rank and Chi-Square p-values to test the equality of Kaplan-Meier survival probabilities and hazard rates (HR) for failure to retain in care for any reason by study arm. RESULTS: There was no significant difference in adherence to PMTCT clinic visits or to ART or in median viral loads between FLC and SOC arms at any follow-up time points. Retention in care through the end of study was high in both arms but significantly higher among participants randomized to FLC (86.7%) compared to SOC (79.3%), p = 0.022. The adjusted HR of visit dropout was 2.4 times greater among participants randomized to SOC compared to FLC (aHR = 2.363, 95% CI: 1.199-4.656, p = 0.013). Median VL remained < 400 copies/ml in both arms at 6 weeks, 6, and 24 months postpartum. Eight of the 431 infants tested at 18 months were HIV positive (1.9%), however, this was not statistically different among mothers enrolled in the FLC arm compared to those in the SOC arm. At 18 months, HIV-free survival of children born to mothers in the FLC arm was significantly higher than that of children born to mothers in the SOC arm. CONCLUSIONS: Our findings suggest that programmatic interventions that provide group support, community-based ART distribution, and income-generation activities may contribute to retention in PMTCT care, HIV-free survival of children born to women living with HIV, and ultimately, to the elimination of mother-to-child HIV transmission (EMTCT). TRIAL REGISTRATION: NCT02515370 (04/08/2015) on ClinicalTrials.gov.

Enhanced Peer-Group strategies to support prevention of Mother-to-Child HIV transmission leads to increased retention in care in Uganda: A Randomized controlled trial.

Introduction: Despite scale up of Option B+, long-term retention of women in HIV care during pregnancy and the postpartum period remains an important challenge. We compared adherence to clinic appointments and antiretroviral therapy (ART) at different follow-up time points between enrolment and 24 months postpartum among pregnant women living with HIV and initiating Option B+ randomized to a peer group support, community-based drug distribution and income-generating intervention called "Friends for Life Circles" (FLCs) versus the standard of care (SOC). Methods: Between 16 May 2016 and 12 September 2017, 540 ART-naïve pregnant women living with HIV at urban and rural health facilities in Uganda were enrolled in the study. Participants were randomized 1:1 to the FLC intervention or SOC and assessed for adherence to prevention of mother to child HIV transmission (PMTCT) clinic appointments at 6 weeks, 12 and 24 months postpartum, self-reported adherence to ART at 6 weeks, 6 and 24 months postpartum validated by plasma HIV-1 RNA viral load (VL) measured at the same time points, and HIV status and HIV-free survival of infants at 18 months postpartum. We used Log-rank and Chi-Square p-values to test the equality of Kaplan-Meier survival probabilities and hazard rates (HR) for failure to retain in care for any reason by study arm. Results: There was no significant difference in adherence to PMTCT clinic visits or to ART or in median viral loads between FLC and SOC arms at any follow-up time points. Retention in care through the end of study was high in both arms but significantly higher among participants randomized to FLC (86.7%) compared to SOC (79.3%), p=0.022. The adjusted HR of visit dropout was 2.5 times greater among participants randomized to SOC compared to FLC (aHR=2.498, 95% CI: 1.417 - 4.406, p=0.002). Median VL remained < 400 copies/ml in both arms at 6 weeks, 6 and 24 months postpartum. Conclusions: Our findings suggest that programmatic interventions that provide group support, community based ART distribution and income-generation activities may contribute to retention in PMTCT care, HIV-free survival of children born to women living with HIV, and to the elimination of mother to child HIV transmission (MTCT).

Twenty years of Prevention of Mother to Child HIV Transmission: research to implementation at a national referral hospital in Uganda.

Background: Over 90% of new paediatric HIV infections are acquired through mother to child transmission. Prevention of mother to child HIV transmission (PMTCT) research in sub-Saharan Africa informed WHO guidelines which enabled implementation of PMTCT programs globally. Objectives: To describe Makerere University-Johns Hopkins University (MU-JHU) perinatal HIV prevention research and implementation of the Mulago National Referral Hospital (MNRH) PMTCT program. Methods: Perinatal HIV prevention studies conducted at MU-JHU between 1997-2016 were summarized. Program aggregated data was extracted and analyzed using STATA 15. Results: In 1999, the HIVNET 012 study demonstrated that single-dose nevirapine (sdNVP) to the mother at onset of labor and to her newborn, reduced MTCT by nearly 50%. In 2016, the PROMISE study documented the safety and efficacy of ART during pregnancy and breastfeeding period. Program implementation at MNRH started in 2000. Uptake of HIV testing increased from 70% to 99% from 2006 onwards. sd NVP was the initial ARV regimen but by 2012, MOH recommended Option B+(triple therapy). MTCT rates reduced from 16.9% in 2001 to 2.3% in 2020. Conclusion: Perinatal HIV prevention clinical trials conducted at MU-JHU provided evidence to inform WHO PMTCT guidelines. MNRH program evaluation demonstrated the significant decline in MTCT rates over the last two decades.

Twenty years of prevention of mother to child HIV transmission: research to implementation at a national referral hospital in Uganda

Background: Over 90% of new paediatric HIV infections are acquired through mother to child transmission. Prevention of mother to child HIV transmission (PMTCT) research in sub-Saharan Africa informed WHO guidelines which enabled implementation of PMTCT programs globally. Objectives: To describe Makerere University-Johns Hopkins University (MU-JHU) perinatal HIV prevention research and implementation of the Mulago National Referral Hospital (MNRH) PMTCT program. Methods: Perinatal HIV prevention studies conducted at MU-JHU between 1997­2016 were summarized. Program aggregated data was extracted and analyzed using STATA 15. Results: In 1999, the HIVNET 012 study demonstrated that single-dose nevirapine (sdNVP) to the mother at onset of labor and to her newborn, reduced MTCT by nearly 50%. In 2016, the PROMISE study documented the safety and efficacy of ART during pregnancy and breastfeeding period. Program implementation at MNRH started in 2000. Uptake of HIV testing increased from 70% to 99% from 2006 onwards. sd NVP was the initial ARV regimen but by 2012, MOH recommended Option B+(triple therapy). MTCT rates reduced from 16.9% in 2001 to 2.3% in 2020. Conclusion: Perinatal HIV prevention clinical trials conducted at MU-JHU provided evidence to inform WHO PMTCT guidelines. MNRH program evaluation demonstrated the significant decline in MTCT rates over the last two decades.

Prevalence of undetectable and suppressed viral load in HIV-infected pregnant women initiating Option B+ in Uganda: an observational study nested within a randomized controlled trial.

BACKGROUND: Viral load (VL) testing is key in monitoring adherence to antiretroviral therapy (ART) and documenting HIV treatment response. As per HIV treatment guidelines in Uganda, the first VL test is recommended 6 months after initiation of ART. Undetectable VL (uVL) at ART initiation may be helpful in detecting elite controllers in the absence of previous ART use. We investigated viral suppression at ART initiation among a cohort of HIV-positive pregnant women enrolled in the Friends for Life Circles (FLC) for Option B+ randomized controlled trial (RCT). METHODS: Pregnant women ≥ 18 years of age testing positive for HIV at their first antenatal care visit and starting on ART Option B+ as per the National PMTCT Program guidelines were enrolled into the FLC for Option B+ RCT in urban Kampala and rural Mityana districts of Uganda. Each participant had whole blood samples collected at enrolment to assess baseline VL. Plasma HIV-1 RNA was quantified using COBAS Ampliprep /COBAS Taqman. Baseline VL below 400 RNA copies/ml was considered as viral suppression while baseline VL below 20 RNA copies/ml was considered uVL. RESULTS: The mean duration from the date of ART initiation to time of sample collection for baseline VL assessment was 4.4 days (SD 3.6). Of the 532 HIV-positive pregnant women enrolled in the FLC for Option B+ study and newly starting Option B+ without a self-reported history of prior ART use, 29 (5.5%) had uVL and 113 (21.4%) had suppressed VL at baseline. There was no association between participants' age, gravidity, marital status, mean monthly income, educational level, disclosure of HIV status to partner, and uVL or viral suppression at baseline. However, non-disclosure of HIV status to any other person was associated with decreased odds of viral suppression at baseline (OR 0.640; 0.416-0.982). CONCLUSION: Twenty-one percent of HIV-positive Ugandan pregnant women initiating ART (Option B+) showed virological suppression at baseline and were presumed to be "elite controllers" or to have misreported being ART-naive. Further studies are needed to better understand the biologic mechanisms of elite controllers among pregnant women as well as to differentiate elite controllers from concealed ART use. Trial Registration The trial was registered as NCT02515370 (04/08/2015) on Clinicaltrials.gov.

Pregnant women, their male partners and health care providers' perceptions of HIV self-testing in Kampala, Uganda: Implications for integration in prevention of mother-to-child transmission programs and scale-up.

BACKGROUND: HIV status awareness is critical for HIV prevention and care but HIV testing rates remain low in Uganda, especially among men. One suggested approach to increase access and utilisation of HIV testing services is HIV self-testing. We explored perceptions of pregnant and lactating women and their male partners who attended antenatal care, and health care providers in a government hospital in Kampala, Uganda, about HIV self-testing for initial or repeat testing for women and their partners during pregnancy and postpartum We draw implications for scaling-up this new testing approach in Uganda. METHODS: This was a qualitative study conducted at Mulago National Referral Hospital, Kampala, Uganda, between April and December 2017. We conducted in-depth interviews with five pregnant or lactating women and their five male partners; five focus group discussions (two with women, two with health workers and one with male partners of women attending antenatal care) and five key informant interviews with health workers providing prevention of mother-to-child HIV transmission (PMTCT) services. Data were analysed using content thematic approach. RESULTS: There was limited awareness about HIV self-testing especially among pregnant or lactating women and their male partners. Study participants mentioned that HIV self-testing would enable people to know their HIV status faster, they thought the approach would be cost- and time-saving compared to health facility-based HIV testing, improve confidentiality and reduce stigma for those who test HIV positive. They expressed however, a general fear that HIV self-testing would lead to harm to self and others in case one tested HIV positive, including suicide, violence among couples, intentional transmission of HIV, and limited linkage to care due to lack of counselling. The likely misinterpretation of HIV test results especially among those with no or limited education, and possible coercion exerted by male partners on their wives were other potential concerns raised about the use of HIV self-testing. CONCLUSIONS: There was limited knowledge about HIV self-testing among pregnant and lactating women, their partners and health workers. While the self-testing modality was perceived to be critical for helping people, especially those in casual and distant relationships, to know their HIV status and that of their partners, most study participants believed that HIV self-testing could potentially result in a multitude of negative outcomes in the absence of pre- and post-test counselling. Successful scale-up and integration of self-testing in HIV programs requires community education, provision of information materials and making self-test kits accessible and affordable, especially in rural areas.

"[Repeat] testing and counseling is one of the key [services] that the government should continue providing": participants' perceptions on extended repeat HIV testing and enhanced counseling (ERHTEC) for primary HIV prevention in pregnant and lactating women in the PRIMAL study, Uganda.

BACKGROUND: The 'Primary HIV Prevention among Pregnant and Lactating Ugandan Women' (PRIMAL) randomized controlled trial aimed to assess an enhanced counseling strategy linked to extended postpartum repeat HIV testing and enhanced counseling among 820 HIV-negative pregnant and lactating women aged 18-49 years and 410 of their male partners to address the first pillar of the WHO Global Strategy for the Prevention of Mother-to-Child HIV transmission (PMTCT). This paper presents findings of qualitative studies aimed at evaluating participants' and service providers' perceptions on the acceptability and feasibility of the intervention and at understanding the effects of the intervention on risk reduction, couple communication, and emotional support from women's partners. METHODS: PRIMAL Study participants were enrolled from two antenatal care clinics and randomized 1:1 to an intervention or control arm. Both arms received repeat sexually transmitted infections (STI) and HIV testing at enrolment, labor and delivery, and at 3, 6, 12, 18 and 24 months postpartum. The intervention consisted of enhanced quarterly counseling on HIV risk reduction, couple communication, family planning and nutrition delivered by study counselors through up to 24 months post-partum. Control participants received repeat standard post-test counseling. Qualitative data were collected from intervention women participants, counsellors and midwives at baseline, midline and end of the study through 18 focus group discussions and 44 key informant interviews. Data analysis followed a thematic approach using framework analysis and a matrix-based system for organizing, reducing, and synthesizing data. RESULTS: At baseline, FGD participants mentioned multiple sexual partners and lack of condom use as the main risks for pregnant and lactating women to acquire HIV. The main reasons for having multiple sexual partners were 1) the cultural practice not to have sex in the late pre-natal and early post-natal period; 2) increased sexual desire during pregnancy; 3) alcohol abuse; 4) poverty; and 5) conflict in couples. Consistent condom use at baseline was limited due to lack of knowledge and low acceptance of condom use in couples. The majority of intervention participants enrolled as couples felt enhanced counselling improved understanding, faithfulness, mutual support and appreciation within their couple. Another benefit mentioned by participants was improvement of couple communication and negotiation, as well as daily decision-making around sexual needs, family planning and condom use. Participants stressed the importance of providing counselling services to all couples. CONCLUSION: This study shows that enhanced individual and couple counselling linked to extended repeat HIV and STI testing and focusing on HIV prevention, couple communication, family planning and nutrition is a feasible and acceptable intervention that could enhance risk reduction programs among pregnant and lactating women. TRIAL REGISTRATION: ClinicalTrials.gov registration number NCT01882998, date of registration 21st June 2013.

Primary HIV prevention in pregnant and lactating Ugandan women: A randomized trial.

BACKGROUND: The 'Primary HIV Prevention among Pregnant and Lactating Ugandan Women' (PRIMAL) study aimed to assess the effectiveness of an enhanced HIV counseling intervention for preventing HIV acquisition among HIV-uninfected mothers during pregnancy and throughout the breastfeeding period. METHODS: We conducted an unblinded randomized control trial between 22 February 2013 and 22 April 2016 to assess the effectiveness of an extended repeat HIV testing and enhanced counseling (ERHTEC) intervention aimed at preventing primary HIV infection among HIV-uninfected pregnant and lactating women in Uganda. HIV-uninfected pregnant women aged 15-49 were enrolled 1:1 individually or in couples together with their partner. Enrolled women and couples were randomized 1:1 to an intervention (ERHTEC) or control (extended repeat HIV testing and standard counseling) group and followed up to 24 months postpartum or six weeks past complete cessation of breastfeeding, whichever came first. Both groups were tested for sexually transmitted infections (STIs) and HIV at enrollment, delivery, 3 and 6 months postpartum and every 6 months thereafter until the end of follow-up. The intervention group received enhanced HIV prevention counseling every 3 months throughout follow-up. The control group received standard counseling at the time of HIV retesting. Both intervention and control couples were offered couple HIV testing and counseling at all study visits. MAIN OUTCOME MEASURES: Frequency of condom use and incidence of HIV, syphilis, gonorrhea, chlamydia and trichomoniasis over follow-up. RESULTS: Between February 2013 and April 2014, we enrolled 820 HIV-uninfected pregnant women presenting for antenatal care individually (n = 410) or in couples (n = 410 women and 410 partners) in one urban and one rural public Ugandan hospital. Women's median age was 24 years (IQR 20-28 years). At baseline, participants did not differ in any socio-demographic, reproductive health, HIV testing history, sexual behavior, medical history or STI status characteristics; 96% (386/402) of couples were tested and counseled for HIV together with their partners at enrolment, 2.1% (7/329) of whom were found to be HIV-infected. Six hundred twenty-five (76%) women completed follow-up as per protocol (S1 Protocol). Women were followed for an average of 1.76 years and cumulated 1,439 women-years of follow-up or 81% of the maximum 1,779 women-years of follow-up assuming no dropouts. Men were followed for an average of 1.72 years. The frequency of consistent condom use and the proportion of women who used condoms over the last 3 months or at last vaginal sex increased substantially over follow-up in both arms, but there were no statistically significant differences in increases between the intervention and control arms. During follow-up, on average 42% (range 36%-46%) of couple partners were counseled together. Between 3.8% and 7.6% of women tested positive at any follow-up visit for any STI including syphilis, gonorrhea, C. trachomatis or T. vaginalis. Four women (two in each arm) and no enrolled men became infected with HIV, representing an overall HIV incidence rate of 0.186 per 100 person-years. Three of the women seroconverters had enrolled individually, one as a couple. At or before seroconversion, all four women reported their partners had extramarital relationships and/or had not disclosed their suspected HIV-infected status. There were no statistically significant differences between study arms for STI or HIV incidences. CONCLUSIONS: A sustained enhanced HIV prevention counseling intervention for up to 2 years postpartum among pregnant and breastfeeding women did not have a statistically significant effect on condom use or HIV incidence among these women. However, in both study arms, condom use increased over follow-up while STI and HIV incidence remained very low when compared to similar cohorts in and outside Uganda, suggesting that repeat HIV testing during breastfeeding, whether with enhanced or standard counseling, may have had an unintended HIV preventive effect among pregnant and lactating women in this setting. Further research is needed to verify this hypothesis. TRIAL REGISTRATION: ClinicalTrials.gov NCT01882998.

Greater involvement of HIV-infected peer-mothers in provision of reproductive health services as "family planning champions" increases referrals and uptake of family planning among HIV-infected mothers.

BACKGROUND: In 2012, Makerere University Johns - Hopkins University, and Mulago National Referral Hospital, with support from the National Institute of Health (under Grant number: NOT AI-01-023) undertook operational research at Mulago National Hospital PMTCT/PNC clinics. The study employed Peer Family Planning Champions to offer health education, counselling, and triage aimed at increasing the identification, referral and family planning (FP) uptake among HIV positive mothers attending the clinic. METHODS: The Peer Champion Intervention to improve FP uptake was introduced into Mulago Hospital PMTCT/PNC clinic, Kampala Uganda. During the intervention period, peers provided additional FP counselling and education; assisted in identification and referral of HIV Positive mothers in need of FP services; and accompanied referred mothers to FP clinics. We compiled and compared the average proportions of mothers in need that were referred and took up FP in the pre-intervention (3 months), intervention (6 months), and post-intervention(3 months) periods using interrupted time series with segmented regression models with an autoregressive term of one. RESULTS: Overall, during the intervention, the proportion of referred mothers in need of FP increased by 30.4 percentage points (P < 0.001), from 52.7 to 83.2 percentage points. FP uptake among mothers in need increased by over 31 percentage points (P < 0.001) from 47.2 to 78.5 percentage points during the intervention. There was a positive non-significant change in the weekly trend of referral ß3 = 2.9 percentage points (P = 0.077) and uptake ß3 = 1.9 percentage points (P = 0.176) during the intervention as compared to the pre-intervention but this was reversed during the post intervention. Over 57% (2494) mothers took up Depo-Provera injectable-FP method during the study. CONCLUSIONS: To support overstrained health care work force in post-natal clinics, peers in trained effective family planning can be a valuable addition to clinic staff in limited-resource settings. The study provides additional evidence on the utilization of peer mothers in HIV care, improves health services uptake including family planning which is a common practice in many donor supported programs. It also provides evidence that may be used to advocate for policy revisions in low-income countries to include peers as support staff especially in busy clinic settings with poor services uptake.

Prevalence and predictors of unknown HIV status among women delivering in Mulago National Referral Hospital, Kampala, Uganda.

INTRODUCTION: Knowledge of a person's HIV status during pregnancy is critical for prevention of mother to child transmission of HIV. OBJECTIVES: To determine the prevalence and factors associated with unknown HIV status among women delivering in Mulago Hospital. METHODS: This was a cross-sectional study of women that had just delivered. The women's demographic characteristics, health seeking behaviour, health system-related factors and knowledge on PMTCT were collected. Fisher's exact test, Wilcoxon rank sum test and logistic regression were used to test associations. RESULTS: The prevalence of unknown HIV status was 2.6% (10/382). Attending ANC at higher level facilities (OR =0.1 95% CI 0.0 - 0.4) and having been counselled for HIV testing during ANC (OR=0.1, 95% CI 0.0 - 0.4) were associated with likelihood of having a known HIV status. Out of the ten women with unknown HIV status, 4/6 who attended ANC in public/government accredited health facilities "opted out" of HIV testing due to personal reasons. Among the four who attended ANC in private clinics, two were not offered HIV testing and one "opted out". CONCLUSION: Most participants had a known HIV status at labour (97%). Private clinics need to be supported to provide free quality HCT services in ANC.

Use of peers, community lay persons and Village Health Team (VHT) members improves six-week postnatal clinic (PNC) follow-up and Early Infant HIV Diagnosis (EID) in urban and rural health units in Uganda: A one-year implementation study.

BACKGROUND: Effective Prevention of Mother to child Transmission of HIV (PMTCT) relies heavily on follow-up of HIV-infected women and infants from antenatal, through postnatal, to the end of the breastfeeding period. In Uganda, postnatal (PNC) follow-up remains below 50 % creating a missed opportunity for linkage to comprehensive HIV care and early infant diagnosis (EID). We evaluated the use of HIV infected peer mothers (peers), community lay persons and Village health team (VHT) members to improve PNC follow up and EID in urban and rural health units. METHODS: Study participants were HIV-infected women recruited from antenatal clinics at three urban clinics (Mulago, Rubaga and Mengo hospitals) and one rural health centre (Mpigi Health centre IV) between January and September 2010. The women were followed through delivery and the mother-infant pairs for the 6-week postnatal visit and up to 14 weeks for EID. Peers, community lay persons and VHT members were identified and trained in basic PMTCT and reproductive health (RH). They were then assigned to study clinic to support and follow study participants, their partners and infants through provision of health education, counseling, home visits, and phone call reminders. Six week PNC attendance was measured as a proportion of mother-infant pairs that returned for the 6-week postnatal follow up visit (5-8 weeks) while EID was measured as the proportion of HIV-exposed live birth that had an HIV test done by 14 weeks of age. Data at baseline (one year before the intervention) was compared with that during the one year study period among study participants and HIV infected women and their HIV-exposed infants in the whole clinic population. RESULTS: A total of 558 HIV-infected pregnant women were recruited for the study, 47 mother-infant pairs were censured before 6 weeks due to stillbirth (14), infant death < 6 weeks (23), death of participant (04) and loss to follow up before delivery (6). 401/511 (78.5 %) of mother-infant pairs returned to the study clinics at six-week, while 441/511 (86.3 %) infants were tested for HIV infection by 14 weeks of age. The baseline six-week PNC follow up was 37.7 % and increased during the study period to 78.5 % and 39.1 % among study participants and whole clinic population respectively, an incremental difference of 39.4 % (P < 0.001). EID increased from a baseline of 53.6 % to 86.3 % and 65.8 % among study and whole clinic population respectively during the study period, an incremental difference of 20.5 % (P < 0.001). CONCLUSIONS: Use of peers, community lay persons and VHT members led to a significant increase in six-week postnatal follow up of HIV infected women and EID among HIV exposed infants in the four study clinics. Our study supports the use of peers to improve early postnatal follow up and EID and should be implemented in other health units to support the PMTCT cascade.

Long-term clinical and immunologic outcomes of HIV-infected women with and without previous exposure to nevirapine.

OBJECTIVES: To determine and compare the clinical and immunologic outcomes for HIV-infected women initiated on antiretroviral therapy (ART), with and without previous exposure to single-dose nevirapine in the MTCT-Plus programme - Kampala, Uganda, from 2003 to 2011. METHODS: Retrospective comparison of prospectively collected programmatic data of clinical and immunologic treatment outcomes among HIV-infected Ugandan women, with and without prior exposure to sdNVP, who received NNRTI-based ART for a median follow-up of 6 years. RESULTS: Of the 408 women in the programme, 289 (70.8%) were started on ART, of whom 205 (70.9%) had prior exposure to sdNVP. Clinical, immunologic and combined (clinical and or immunologic) treatment failure occurred in 29 (10.0%), 132 (45.7%) and 142 (49.1%) women, respectively. There was no significant difference in the distribution of time to immunologic failure for women by exposure to sdNVP (log-rank P = 0.98). In Cox proportional hazard modelling, exposure to sdNVP was not associated with immunologic failure [adjusted hazard ratio (HR) = 0.89, 95% confidence interval (CI): 0.61-1.30]. CD4 count >100 cells/mm(3) at initiation was associated with reduced incidence of immunologic failure in adjusted analyses (HR = 0.32, 95% CI: 0.22-0.48). CONCLUSIONS: HIV-infected Ugandan women initiated on an NVP-based ART regimen had similar immunologic treatment outcomes irrespective of previous NVP exposure. CD4 cell count prior to initiating HAART was a key prognostic factor for successful long-term immunologic treatment outcomes. In poor settings, regular follow-up of patients on HAART with adequate counselling to promote adherence and safe disclosure may promote low clinical failure rates.

The impact of maternal highly active antiretroviral therapy and short-course combination antiretrovirals for prevention of mother-to-child transmission on early infant infection rates at the Mulago national referral hospital in Kampala, Uganda, January 2007 to May 2009.

BACKGROUND: Early HIV infant diagnosis and treatment have been shown to dramatically improve survival in infants. Despite these findings, infants accessing HIV diagnosis and treatment remain low in Uganda. We describe the antiretroviral (ARV) drugs given in the Mulago Hospital prevention of mother-to-child transmission (PMTCT) program from January 2007 to May 2009 and its impact on early infant HIV infection rates. METHODS: Pregnant women identified as HIV infected in the Mulago antenatal clinics received one of the following regimens: short-course ARV prophylaxis plus single-dose nevirapine (sdNVP) in labor, highly active antiretroviral therapy (HAART), or sdNVP if they presented in labor. Infants received sdNVP and zidovudine (ZDV) for 1 week. Infants HIV diagnosis was done from 6 weeks after delivery. RESULTS: 62.3% of HIV-infected women received combination ARVs, including HAART. Early infection rates were highest among infants with no maternal ARV [36.4; 95% confidence interval (CI): 17.2 to 59.3] or only sdNVP (11.2; 95% CI: 8.1 to 14.8). Similar rates were observed for the group that took short-course ARVs, ZDV/sdNVP (4.6; 95% CI: 3.2 to 6.4), and ZDV/lamivudine/sdNVP (4.9; 95% CI: 3.1 to 7.2) and lowest rates for those that took HAART (1.7: 95% CI: 0.8 to 2.8). Overall infection rate was 5.0% (95% CI: 4.1 to 5.9). CONCLUSIONS: Findings indicate low rates of infant infection for mothers receiving combination ARVs. These findings demonstrate that provision of combination ARV for PMTCT is feasible and effective in busy referral hospital's PMTCT programs in resource-limited settings.